Glycocalyx degradation leads to blood–brain barrier dysfunction and brain edema after asphyxia cardiac arrest in rats

Zhu, Jiajia; Li, Xing; Yin, Jia; Y, Hu; Gu, Yong; Pan, Suyue

doi:10.1177/0271678x17726062

Cited by 81 publications

(106 citation statements)

References 37 publications

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“…We also demonstrated that the PMPC polymer chains target the scavenger receptor B1 (SRB1) (35), also expressed by BECs (33). We know from the literature (36,37) that endothelial cells (38,39), and BECs (37) in particular, express high levels of the glycocalyx syndecan 4. On the basis of this information, we thus reconstructed a possible arrangement of LRP1, SRB1, and syndecan 4 proteins on a stereotypical BEC membrane.…”

Section: The Case Studymentioning

confidence: 72%

On the design of precision nanomedicines

2020

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Tight control on the selectivity of nanoparticles' interaction with biological systems is paramount for the development of targeted therapies. However, the large number of tunable parameters makes it difficult to identify optimal design "sweet spots" without guiding principles. Here, we combine superselectivity theory with soft matter physics into a unified theoretical framework and we prove its validity using blood brain barrier cells as target. We apply our approach to polymersomes functionalized with targeting ligands to identify the most selective combination of parameters in terms of particle size, brush length and density, as well as tether length, affinity, and ligand number. We show that the combination of multivalent interactions into multiplexed systems enable interaction as a function of the cell phenotype, that is, which receptors are expressed. We thus propose the design of a "bar-coding" targeting approach that can be tailor-made to unique cell populations enabling personalized therapies.

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Section: The Case Studymentioning

confidence: 72%

On the design of precision nanomedicines

2020

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“…While small dyes such as fluorescein (376 daltons) and Alexa Fluor (643 daltons) permeate the glycocalyx, dextrans (40–150 kD) penetrate <60% of its volume (Kutuzov et al, 2018). In disease, glycocalyx degradation is associated with more severe BBB leakage in models of multiple sclerosis (MS) and cardiac arrest (DellaValle et al, 2018; Zhu et al, 2018).…”

Section: The Nvumentioning

confidence: 99%

The blood–brain barrier in health and disease: Important unanswered questions

Profaci

Munji

Pulido

et al. 2020

Journal of Experimental Medicine

394

301

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The blood vessels vascularizing the central nervous system exhibit a series of distinct properties that tightly control the movement of ions, molecules, and cells between the blood and the parenchyma. This “blood–brain barrier” is initiated during angiogenesis via signals from the surrounding neural environment, and its integrity remains vital for homeostasis and neural protection throughout life. Blood–brain barrier dysfunction contributes to pathology in a range of neurological conditions including multiple sclerosis, stroke, and epilepsy, and has also been implicated in neurodegenerative diseases such as Alzheimer’s disease. This review will discuss current knowledge and key unanswered questions regarding the blood–brain barrier in health and disease.

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“…We also demonstrated the poly[2-(methacryloyloxy)ethyl phosphorylcholine] (PMPC) polymer chains target the scavenger receptor B1 (SRB1) (36), also expressed by brain endothelial cells (34). We know from the literature (37,38) that endothelial cells (39,40), and BECs (38) in particular, express high level of the glycocalyx syndecan 4. Based on these information, we thus reconstructed a possible arrangement of LRP1, SRB1 and syndecan 4 proteins on a stereotypical BEC membrane.…”

Section: Theorymentioning

confidence: 90%

On the design of precision nanomedicines

Tian¹,

Agioletti-Uberti²,

Battaglia

2019

Preprint

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TeaserWe proposed the design of nanomedicines that target cells phenotypically enabling binding only when a precise receptor(s) composition is present. AbstractTight control on the selectivity of nanoparticles' interaction with biological systems is paramount for the development of targeted therapies. However, the large number of synthetically tunable parameters makes it difficult to identify optimal design ``sweet spots'' without rational guiding principles. Here we address this problem combining super-selectivity theory (SST) with analytical models from soft matter and polymer physics into a unified theoretical framework. Starting from an archetypal polymersome functionalized with targeting ligands, we use our model to identify the most selective combination of parameters in terms of particle size, brush polymerization degree and grafting density, as well as tether length, binding affinity and ligands number. We further show how to combine multivalent interactions into multiplexed systems which act holistically as a function of the density of more than one receptor type, so as to achieve binding only when multiple receptors are expressed above a threshold density. We show that theory can be used to effectively fit experimental data and, hence confirming its suitability. We thus propose the design of "barcoding" targeting approach that can be tailor-made to unique cell populations enabling personalized therapies.

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Glycocalyx degradation leads to blood–brain barrier dysfunction and brain edema after asphyxia cardiac arrest in rats

Cited by 81 publications

References 37 publications

On the design of precision nanomedicines

On the design of precision nanomedicines

The blood–brain barrier in health and disease: Important unanswered questions

On the design of precision nanomedicines

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